Licochalcone A promotes autophagy to ameliorate NAFLD by inhibiting the mTOR and regulating ULK1/Beclin1/VPS34 pathway.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is one of the most commonly used Chinese medicines. Licochalcone A (Lico A) is a flavonoid, which is one of the main components extracted from licorice. It has a variety of pharmacological activities such as improving glucose and lipid metabolism. However, the therapeutic efficacy of Lico A against non-alcoholic fatty liver disease (NAFLD) and the underlying mechanism of this action remains unclear. AIM OF THE STUDY: The aim of this study was to investigate the interventional effect and mechanism of action of Licochalcone A in NAFLD by combining in vivo and in vitro experiments. MATERIALS AND METHODS: NAFLD mouse model was established with MCD feed, and an in vitro cell model was established with free fatty acid (FFA) formulated with palmitic acid (PA) and oleic acid (OA). After stimulation with Licochalcone A, the changes in the in vivo and in vitro models were observed to clarify whether Licochalcone A has an ameliorative effect on NAFLD. The mechanism of action of Licochalcone A in ameliorating NAFLD was further verified by transcriptomics, mTOR-related protein detection, agonist and inhibitor experiments. RESULTS: Compared with the model group, the number of intracellular lipid vacuoles and red fat droplets was reduced in the Lico A group, and the size of adipocytes was reduced. Meanwhile, the liver function and lipid indexes such as AST, ALT, TG, CHO, HDL-C and LDL-C were reduced. mTOR expression level was reduced, and the expression levels of ULK1, Beclin-1, VPS34, Atg5 and Atg12 were increased. CONCLUSION: Licochalcone A alleviates NAFLD, reduces hepatic lipid deposition and enhances liver function. Its mechanism of action is related to the inhibition of mTOR expression and regulation of ULK1/Beclin-1/VPS34 pathway thereby promoting autophagy.